Lead Discovery Services

WuXi Biology offers compound screening and profiling services to assist our clients for lead identification and optimization. We focus our efforts on lead selection and assessment to gear at providing clients with reliable and accurate information through scientific procedures. Panels of profiling assays offer an integrated tool for clients to better characterize and optimize the pharmacology and toxicity profiles of their lead compounds. Our services include:

  • Biochemical assays
  • Cell-based functional assays (i.e. in various target classes such as GPCRs, enzymes, ion channels and transporters)
  • Pathway-based cellular phenotypic assays
  • High-content assays
  • in vitro ADME assays
  • Off-target assays
  • in vitro safety
  • in vivo pharmacology
  • Pharmacokinetics
  • Medicinal Chemistry / Drug Design
  • Computational Chemistry
  • Bioinformatics

In vitro ADME profiling involves assays on cell permeability, plasma protein binding, cytochrome P450 subtype inhibition, metabolic stability in hepatocytes and liver subcellular fractions, plasma stability and cytotoxicity. In vivo PK studies include studies in various dosing routes (e.g. oral, subcutaneous, i.v. i.p, etc.) in different tissues and specimens on most small and large animals, followed by the full service of bioanalytical analysis and data reports.

We offer various disease models in different therapeutic areas, such as metabolic disorders, oncology, CNS (pain, memory/learning, stress) and inflammation to provide one-stop biological services with pharmacology and pathology.


Cell-based functional assays

Imaging and High Content Assays/Screening (HCA/HCS)

We offer compound screening and profiling services to assist our clients for lead identification and optimization. We focus our efforts on lead selection and assessment to gear at providing clients with reliable and accurate information through scientific procedures. Panels of profiling assays including biochemical assays and cell-based functional assays (i.e. in various target classes such as GPCRs, enzymes, ion channels and transporters), in vitro ADMET assays and pathway-based cellular phenotypic assays as well as high-content assays offer an integrated tool for clients to better characterize and optimize the pharmacology and toxicity profiles of their lead compounds.

  • Genotoxicity and cytotoxicity (micronucleus test; tube formation; caspase activation)
  • Cell signaling and transcription factors
  • Cell proliferation and cell cycles
  • Apoptosis and viability
  • Kinase translocation and GPCRs redistribution
  • Morphological and phenotypic changes
Imaging Platform
  • Automated cell imaging systems, ImageXpressMICRO™ (Molecular Devices)
  • Powerful analysis software: MetaXpress™ Software and Assay Application Modules
  • AcuityXpress™ Cellular Informatics Software
  • Advanced large scale data storage and IT support
Service Features
  • Subcellular localization and quantitation of the cellular targets
  • Multiplexing capabilities: multiple data points from a single assay well
  • Parallel analysis of functional activity and cytotoxicity in one assay well
  • High sensitivity (nuclei staining allows for normalization of cellular signals against cell number)
  • Measurement of individual cell responses in the heterogeneous cell populations
  • Application of drug to live cells may indicate side-effects at the early stages of drug development
  • Cell based assays provide a biologically relevant assessment of compound functional activity
  • Robust and cost-effective assays
  • Minimum compound requirement (96 or 384-well plate format)

Compound Profiling

Pharmacology profiling is an invaluable tool for lead compound screening, optimization and candidate prioritization. Analysis of compound profile data identifies off-target interactions that can help predict potential side-effects and safety issues of compounds under development before they progress to the more costly stages of preclinical and clinical trials. WuXi Biology offers comprehensive profiling services to meet our clients’ drug discovery & development needs.

Our compound profiling service include:

GPCRs

  • Panels of 20, 30, 60 GPCRs for selectivity screening
  • Cell-based functional assays, membrane prep binding assays or GTPγS binding assays

Enzymes

  • Repeat dose study
  • NOAEL (no observable adverse effect level) determination

ADME

  • Plasma protein binding
  • Metabolic stability
  • Permeability (Caco-2)
  • CYPs inhibition
  • Human CYP3A4 induction cell based assay
  • Human CYP1A induction cell based assay
  • P-gp inhibition cell based assay

in vitro Toxicity

  • hERG assay (patch-clamp; binding assays)
  • Ames test, micronucleus test
  • Hepatotoxicity
  • Cytotoxic ATP depletion assay
  • Mitochondria toxicity

Functional Cell-based Assays

  • High content assays
  • Phenotypic cellular assays

in vitro toxicology studies

We provide robust and rapid in vitro toxicity screening approaches to identify compound liabilities and STR (structure toxicity relationship) associated with new chemical entities (NCEs) to help our clients to select and optimize NCE in an early drug discovery stage. Fast turnaround results from multiple assays and dose-response profiles allow our clients to understand the potential toxicity of compounds and select compounds with higher probability of success. Most of these assays are high throughput systems (eg 384 plate format) that use small amounts of compound with fast data turnaround (eg. one week) and identify adverse effects to predict toxicity both in animals and humans in order to speed up the process of early drug discovery.

  • Hepatotoxicity
    • Hepatocyte cell viability
    • Steatosis and phospholipidosis
    • Enzyme induction

  • Cytotoxicity
    • ATP content assay
    • HTS method available
    • LDH assayMTT assay

Testing available for HepG2 cells, hepatocyte, astrocytes, neuron cells and other cell lines.

  • Mitochondrial toxicity
    • Fluorescence-based oxygen consumption assay
    • Membrane potential transition (MPT)

  • Drug-drug interaction
    • Human CYP1A induction cell based assay
    • P-gp inhibition cell based assay
  • Genotoxicity
    • Ames Test
    • Micronucleus test (manual / automatic)

  • Cardiac Toxicity
    • hERGs patch clamp
    • hERGs binding assay

In Vivo Pharmacology

WuXi Biology provides preclinical services and tailored solutions to advance your drug candidate selection in multiple disease areas.


Drug Metabolism and Pharmacokinetics (PK-PD)

WuXi Biology consists of experienced scientists who design the best strategies and protocols to suit our client’s needs for their lead optimizations and preclinical candidate selections. The studies are performed under strict guidelines by highly trained and experienced scientists. Our goal is to meet our client’s goal of superior cost, quality, speed and service.

Our services include:

  • In vivo PK and TK
  • Protein Binding
  • Plasma Stability
  • Caco-2 Cell Permeability
  • Blood Cell Partitioning
  • In Vitro Metabolism
  • Metabolite Identification
  • Mass Balance
  • Bioanalytical
  • Solubility and Stability
  • Formulation Test